Date of Award
1-1-2019
Document Type
Thesis
Degree Name
M.S. in Chemistry
First Advisor
Randy M. Wadkins
Second Advisor
Saumen Chakraborty
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Alternative DNA structures are likely to form from Watson-Crick B-form DNA when antitumor drug known to bind DNA loops -- can affect the iM structure. Our results demonstrate as an i-motif (iM). While both structures are known to exist in vivo they are energetically uphill can utilize intercalating cytosine-cytosine base pairing to form a four-stranded structure known controlled by alternative DNA structures like G4s and iMs. especially during processes that involve superhelical duress. A guanosine rich strand can form a facilitate their stabilization. In this report we present data on how 7-aminoactinomycin D -- an formation. Earlier it was believed that iMs required slightly acidic conditions (pH ≤ 6) for four-stranded structure known as a G-quadruplex (G4). The complimentary cytosine rich strand from double strand DNA (dsDNA) meaning that additional factors are needed to facilitate their of ~7. Additionally loop regions of iMs have been implicated in their thermal and pH-dependent shift the pKa of the iM (the pH at which 50% of the iM is folded) nearer to the physiological pH small molecules may be a promising way to therapeutically regulate expression of genes stability. Small molecules such as polyamines and larger molecules like proteins can interact structure stabilization. However crowding agents like polyethylene glycols and dextrans can that a small molecule antitumor drug can stabilize or destabilize iMs by simultaneously changing there is an asymmetric distribution of guanosine and cytosine on opposite DNA strands thermodynamic properties including Tm pKa and ΔG°37 °C. Our results suggest that the use of with iMs by binding to their loops suggesting that additional biochemical factors may also facilitate their stabilization. In this report, we present data on how 7-aminoactinomycin D -- an antitumor drug known to bind DNA loops -- can affect the iM structure. Our results demonstrate that a small molecule antitumor drug can stabilize or destabilize iMs by simultaneously changing thermodynamic properties including Tm, pKa, and ΔG°37 °C. Our results suggest that the use of small molecules may be a promising way to therapeutically regulate expression of genes controlled by alternative DNA structures like G4s and iMs.
Recommended Citation
Parmely, Justin Lane, "Stabilization of DNA i-motif structures by 7-aminoactinomycin D, an anti-tumor drug" (2019). Electronic Theses and Dissertations. 1958.
https://egrove.olemiss.edu/etd/1958